The therapeutics of parkinsonism and related neurological disorders has been the goal of projects assessing the efficacy and safety of new drugs in clinical studies. These investigations have provided insight into biochemical and physiological disturbances underlying movement disorders. Conclusions reached over the past year include: (1) two new ergot derivatives, lisuride and pergolide, have comparable clinical profiles against parkinsonism despite their pharmacological differences. Our pharmacokinetic studies with lisuride offer explanations for variability in effects of the drug; (2) tyrosine hydroxylase cofactor, deficient in parkinsonism, produced increased dopamine synthesis in animals. However, parenteral administration to parkinsonian patients was without benefit; (3) two movement disorders with parkinsonian features but generally without response to L-DOPA, dystonia and progressive supranuclear palsy, have responded in some instances with dopaminergic ergot therapy; (4) clonidine therapy may be effective in essential tremor. Peripheral adrenergic mechanisms do not differ from normal, as shown by isoproterenol testing; (5) binding studies show other neurotransmitter substances (in addition to dopamine) to be decreased in parkinsonian brain.